AlicyclicsAliphatic compounds containing rings, cycloalkanes, cycloalkyl halides, cycloalkyl alcohols, cyclic ethers, cycloalkenes, cycloalkadienes, etc.

Cycloalkanes

H2C

H2CCH2

H2C

H2C CH2

CH2 H2C

H2C CH2

CH2

H2C H2C

H2C CH2

CH2

CH2

H2C

cyclopropane cyclobutane cyclopentane cyclohexane

CH3

BrBr Br Br

CH3

H3C

methylcyclopentane 1,1-dimethylcyclobutane

trans-1,2-dibromocyclohexane

Br

Br

HO

HO

HO OHHO OH

cis-1,2-cyclohexanediol

cyclopentene 3-methylcyclohexene 1,3-cyclobutadiene

1

2

3

4

5

6

cycloalkenes

bicyclo[2.2.2]octane bicyclo[3.2.0]heptane

OH

OCH2CH3

cyclohexanol ethyl cyclopentyl ether

cyclohexyl alcohol

Cycloalkanes, syntheses:

A. Modification of a ring compound:

1. reduction of cycloalkene

2. reduction of cyclic halide

a) hydrolysis of Grignard reagent

b) active metal & acid

3. Corey House

B. Ring closures

A. Modification of a cyclic compound:

Br

Br

H2, Ni

Sn, HCl

Mg; then H2O

Br Li2

CuLi

Li CuI

+ CH3CH2-Br CH2CH3

must be 1o

Corey-House

B. ring closures

CH2=CH2 + CH2CO, hv

Br-CH2CH2CH2CH2CH2-Br + Zn

etc.

cycloalkanes, reactions:

1. halogenation

2. combustion

3. cracking

4. exceptions

ClCl2, heat

+ HCl

exceptions:

H2, Ni, 80o

CH3CH2CH3

Cl2, FeCl3

Cl-CH2CH2CH2-Cl

H2O, H+

CH3CH2CH2-OH

conc. H2SO4

CH3CH2CH2-OSO3H

HI CH3CH2CH2-I

exceptions (cont.)

+ H2, Ni, 200o CH3CH2CH2CH3

??????????

internal bond deviation heat of

angles from 109.5 combustion

60o -49.5o 166.6

90o -19.5o 164.0

108o -1.5o 158.7

Cyclopropane undergoes addition reactions that other cycloalkanes and alkanes do not. This is because of angle strain in the small ring. Because the bond angles are less than the optimal 109.5o for maximum overlap, the bonds are weaker than normal carbon-carbon single bonds and can be added to.

Cyclobutane has angle strain that is less than that for cyclopropane, reacts with H2/Ni at a higher temperature, but does not react like cylcopropane in the other exceptional reactions.

internal bond deviation heat of

angles from 109.5 combustion

60o -49.5o 166.6

90o -19.5o 164.0

108o -1.5o 158.7

120o +11.5o 157.4

128.5o +19o 158.3

135o +25.5o 158.6

Cyclohexane does not have any angle strain! It isn’t a flat molecule. By rotating about the carbon-carbon bonds, it can achieve 109.5o bond angles.

chair twist boat

boat

conformations of cyclohexane

The chair conformation of cyclohexane is free of both angle strain and torsional strain (deviation from staggered). This is the most stable conformation.

The boat conformation is free of angle strain, but has a great deal of torsional strain (eclipsed). To relieve the strain, it twists slightly to form the twist boat:

a a

aa

a

a

e

ee

ee

e

a = axial positions in the chair conformation

e = equatorial positions

CH3

H3C

CH3 in axial position CH3 in equatorial position

is more stable

O

H

HO

H

HO

H

OHOHH H

OH

O

H

HO

H

HO

H

HOHH OH

OHCHO

OHH

HHO

OHH

OHH

CH2OH

beta-D-glucose alpha-D-glucose

all groups equatorial one group forced to be axial

more stable

Cycloalkenes, syntheses:

A. Modification of a ring compound:

1) dehydrohalogenation of an alkyl halide

2) dehydration of an alcohol

3) dehalogenation of vicinal dihalides

(B. Ring closures)

OH

Br

Br

Cl KOH(alc)

H+, Δ

Zn

cyclohexene

Cycloalkenes, reactions:

1. addition of H2 10. hydroboration-oxid.

2. addition of X2 11. addition of free radicals

3. addition of HX 12. polymerization

4. addition of H2SO4 13. addition of carbenes

5. addition of H2O,H+ 14. epoxidation

6. addition of X2 + H2O 15. hydroxylation

7. dimerization 16. allylic halogenation

8. alkylation 17. ozonolysis

9. oxymerc-demerc. 18. vigorous oxidation

Br

Br

trans-1,2-dibromocyclohexane

H2, Pt

Br2, CCl4

H2C

H2CCH2

CH

C

H2C CH3

+ HBr

H2C

H2CCH2

CH2

C

H2C CH3

3o carbocation

Br H2C

H2CCH2

CH2

C

H2C

Br

CH3

Br

OSO3H

OH

HBr

H2SO4

H2O, H+

Markovnikov orientation

OH

Br

+

+

Br2 (aq.)

H+, dimer.

HF, 0o

OH

OH

H2O, Hg(OAc)2 NaBH4

(BH3)2 H2O2, NaOH

Markovnikov

anti Markovnikov

n

Br

O

HBr, peroxides

polymerization

CH2CO, hν

Peroxybenzoic acid

OH

OH

OH

OH

Br

cis-1,2-cyclohexanediol

trans-1,2-cyclohexanediol

KMnO4

HCO3H

Br2, heat

O=CHCH2CH2CH2CH2CH=O

HO2CCH2CH2CH2CH2CO2H

O3 H2O,Zn

KMnO4, heat

Br2 KMnO4 HCO3H

Br HO OH HOBr OH

anti syn anti

stereoselective

cyclic alcohols, halides, ethers as expected:

OH

OH

OH

HO

ONa

Br

O

H3CC

O

O

PBr3

Na

CH3COOH +H+

NaOCl

O

Br

Cl MgCl

I2

NaOH2o alkyl halide => E2

Mg H2O

conc. HI, heat

O

O

1,4-dioxane

conc. HBr, heat2 Br-CH2CH2-Br

Alicyclic compounds are chemically like their open chain analogs. The exceptions are for small ring compounds where angle strain may give rise to reactions that are not typical of other molecules.

Epoxides:

CH2H2CO

CHH2CO

CH3 O

O

ethylene oxide propylene oxide cyclopentene oxide

(oxirane) (methyloxirane)

C6H5CO3H

Synthesis:

β-butylene oxidecis-2-butene

epoxides, reactions:

1) acid catalyzed addition

CH2H2CO

CH2H2CO

CH2H2CO

H2O, H+

CH3CH2OH, H+

HBr

OHCH2CH2

OH

OHCH3CH2-O-CH2CH2

OHCH2CH2

Br

CH2H2CO

CH2H2CO

CH2H2CO

CH2H2CO

NaOH, H2O

NaOCH2CH3

CH3CH2OH

NH3

1. CH3CH2MgBr

2. H2O

OHCH2CH2

OH

CH3CH2-O-CH2CH2-OH

H2N-CH2CH2-OH

CH3CH2CH2CH2-OH

2. Base catalyzed addition

CCO

+ H CCOH

CCOH

+ :ZHRDS

C C

ZH

OH

C C

ZH

OH

C C

Z

OH

+ H

1)

2)

3)

mechanism for acid catalyzed addition to an epoxide

mechanism for base-catalyzed addition to an epoxide:

CCO

C C

Z

OH

1)

2)

+ Z C C

O

ZRDS

C C

O

Z+ HZ + Z

acid catalyzed addition to unsymmetric epoxides?

CH2CHO

H3C

CH2CHO

H3C

OH+ H2O, H+ CH3CHCH2

OH

which oxygen in the product came from the water?

+ H218O, H+

18OHCH3CHCH2

OH

CH2CHO

H3C

CH2CHO

H3C

CH3

O+ CH3OH, H+ CH3CHCH2

OH

Br+ HBr CH3CHCH2

OH

CH2CHO

H3C

CH2CHO

H3C

CH2CHO

H3C

Base?

18OH+ Na18OH, H2

18O CH3CHCH2

OH

NH2

+ NH3 CH3CHCH2

OH

OCH3 + CH3OH, CH3ONa CH3CHCH2

OH

CH2CHO

H3C

CH2CHO

H3C

Acid:

Base:

Z+ HZ CH3CHCH2

OH

Z+ Z-, HZ CH3CHCH2

OH

“variable transition state”

Z

acid: — C — C —

OH

δ+

δ+

‡

base: Z

— C — C —

Oδ-

‡

Bond breaking is occurring faster than bond making, making the carbon slightly positive.

C δ+ : 3o > 2o > 1o

Bond breaking is occurring at the same time as bond breaking, there is no charge on the carbon. Steric factors are most important: 1o > 2o > 3o

CH2CHO

H3C

CH2CHO

H3C

Acid:

Base:

Z+ HZ CH3CHCH2

OH

Z+ Z-, HZ CH3CHCH2

OH

Cδ+: Z to 2o carbon

steric factors: Z to 1o carbon